Method of preventing infection by coccidia by employing a bromoalkene



Patented Feb. 26, 1952 METHOD OF PREVENTING INFECTION BY COCCIDIA BY EMPLOYING A BROMO- ALKENE Alfred E. Doty, Saginaw, Julius E. Johnson, Jr., Midland, Dorsey R. Mussell, Clare, and Mark A. Wolf, Midland, Mich., assignors to The Dow Chemical Company, Midland, Mich, a corporation of Delaware No Drawing. Application March 14, 1947,

Serial No. 734,874

This invention relates to the control of parasitic organisms and is particularly concerned with a method for preventing the infection of domestic animals and poultry by parasitic organisms.

Poultry and domestic animals are subject to attack by a wide variety of animal and bacterial organisms. Internal parasites alone cause millions of dollars in losses annually. Much of this difi'iculty from infections, both internal and external, is directly attributable to contact by the animal or bird with infected soil, litter, and pen or housing surfaces, or excreta, or ingestion of food contaminated thereby. The minimizing of such infections by controllin the responsible organisms present in possible sources of contamination would greatly reduce present day losses.

Also, the prevention of initial infection is much to be preferred over the later medication of animals in diseased condition which could and should have been avoided. The desirability and need for the development of new and improved techniques and methods for reducing animal and poultry losses from parasitic organisms is evident.

It is an object of the present invention to provide a method for the prevention of infection by parasitic organisms of domestic animals and poultry. It is a'further object to supply a method which will accomplish such desirable result by controlling the organisms, their eggs, spores and other intermediate life forms before the latter accomplish the infection of the animal or bird. An additional object is to provide a method for preventing infection of domestic animals and poultry which method will provide for the disinfection of possible sources of contamination normally associated with such animals and poultry. Other objects of the invention will become apparent from the following specification and claims.

. According to the present invention, it has been treated with a synthetic bromo-alkene .of high vapor pressure and having the formula CnHZn-mBIa:

wherein n is an integer from 3 to 4, inclusive, and a: is an integer from 1 to 2, inclusive. The compounds of the foregoing formula have been found to be very toxic against protozoal, fungal,

bacterial, and related organisms, and their inter--- 5 Claims. (01. 16722) mediate life stages, and to exert a lethal action much more rapidly and at lower toxicant concentrations than most other synthetic organic compounds of related chemical structure.

The bromo-alkene compounds employed in the method of the present invention, all are either liquids or low melting solids. For example, allyl bromide is a liquid boiling at '707l C. 1.3-dibromo-propene is a liquid boilin at 156 C. 1.4-dibromo-butene-2 is a solid melting at 53 C. Each of the compounds has both a high vapor pressure and high vapor density whereby their vapors tend to penetrate into cracks and crevices, and through soil and litter to accomplish a more thorough control of organisms than could be accomplished with lighter and more volatile fumigant materials. The compounds are characterized by pungent and penetrating odors, and are somewhat toxic to warmblooded animals. It is desirable that any enclosure in which the compounds have been employed be well aired before being re-utilized as an animal or poultry pen or coop. Reasonable care should be exercised in handling the compounds as they are irritating to the skin and mucous membranes of humans. The compounds do not leave residues toxic to domestic animals and poultry, but vaporize completely and cleanly within a reasonable time.

A wide range of organisms have been found to be controlled by operating in accordance with the method of the present invention. Representative of the parasites afiected are protozoal organisms, such as coccidia; pathogenic bacteria, such as Salmonella pullorum, Eberthella typhosa, and Staphylococcus aureus; nema and annelids, such as cecal worms; trematodes, such as liver flukes; cestodes such as Taem'a cestz'cillus; etc. The method is also effective for the control of certain diseases by destruction of the soil borne vector of the disease. For example, the disinfection of premises to control cecal worm eggs would be effective in the control of blackhead in turkeys. Here, the causative organism is Histomonas meleagridz's which is harbored in the cecal worm 'egg.

It is to be emphasized that the present invention is not concerned with any operation wherein;the effective agent is to be ingested by the animal. The control of the organisms, as listed above, is accomplished by treatment of the soil, litter, housing, and other surfaces normally contacted by the animal or fowl,;and in many instances operates by control of the eggs, spores, or other intermediate life stage of the organisms.

nied by space fumigation. In such operation, the

toxicant may simply be introduced into the house, pen, coop, chamber or other building tobe disinfected and permitted to vaporize slowly over a considerable period of time. In a further modification, the bromo-alkene may be heated or otherwise manipulated to cause a quick vaporization.

Another mode of operation consists of employing the bromo-alkene as a constituent of a liquid composition. Such composit on ma applied by spraying Or sprinkl ir'ig. When proceeding in this fashion, the toxicant may be dissolved or dispersed in an organic solvent to produce a s ray mixture of any aesiijd concentration. Such solution or the bfoifid-alkn itself may be dispersed in water" to produce emulsion-type compositions adapted to be applied to the soil, litter, or other surfaces to be contacted by the animal or bird.

A further manner in which the toxicant may be applied is by injection or the toxicant, where liquid, or of a Suitable solution of dispersion of the toxicant beldvv the surface of th soil, utter, O1 bedding, and at spaced intervals so as to accomplish the building up 6f a lethal concentration Of the toxicant in the zone of infection.

The toxicant may also be compounded to produce an aerosol, a suitable propeuent, such as Freon, methyl chloride, or methyl bromide. An optional constituent of the mixture in the aerosol is a liquid carrier or blending agent. Freon is a (imitators-methane. I

A further and preferred mode of operation is to disperse the bromo-alkenin and on a finelydivided carrier to produce a dust mixture. such product may be sprinkled ordii st'ed upon infected surfaces or may be worked into soil litter, and the like to accomplish the desired controlof parasitic organisms and their intermediate life stages. 7v

In connection with the treatment of soil, litter, bedding, and the like, it is to be understood that such infected surfaces and areas subsequent to treatment may be blanketed with tarpaulins or other vapor-confining coverings, so as to en--v sure the prolonged contact of the chemical and its vapors with the organisms to be controlled. A modification of this procedure comprises sprinkling or spraying the surface of soil, litter,

and the like with water immediately following treatment with the toxicant to accomplish the control different organisms vary considerably. In the operation of the invention, any lethal concentration of the bromo-alkene may be employed, the exact proportion being dependent upon the organisms to be controlled and the conditions un,-

der which control is to be accomplished. In con nection with the treatment of soil, littenfancl the.

like, it has been found that about 0.5 gram per square foot gives an adequate control. However, with certain compounds and organisms, much lower concentrations are effective. For example, in the control of coccidia 1-.-3-dibromo-propene is effective at 0.3 gram per square foot, and 1.4- dibromo-butene-2 at 0.25 gram per square foot. In space fumigation operations, good control of coccidial infection in chickens has been obtained when the pens, houses, and premises have been fumigated with as little as 0.125 pound of 1.3- dibromo-propene per 1000 cubic feet. In practice it is suggested that at least 0.2 pound of toxicant per 1000 cubic feet be employed.

The proportions of toxicant employed in the various spray and dust compositions are not critical. Thus a spray may contain from a fraction of 1 percent of bromo-alkene to as much as 40 or 50 percent by weight of the toxicant. Here again, the exact manner of application is largely controlling. In injection operations for the treatment of soil and litten'liquid compositions containing from about 5 to about 20 percent of the toxicant have been found satisfactory.

Dust compositions may vary in concentration from about 0.5 percent to as high as 20 percent or higher by weight of toxicant. Among the controlling factors here are the manner in which the composition is to be sprinkled or dusted or worked into the soil or litter and possible objections to the presence in and on the treated surfaces of excesses of finely-divided dust carrier.

Any suitable solvent or other liquid may be employed as carrier for the toxicants in accordance with the method herein described. Thus, the bromo-alkenes may be emulsified or otherwise dis-' persed in water. Similarly, such solvents as carbon tetrachloride, chloroform, ethylene dichlo-' ride, propylene dichloride, chloro-benzene, xylene, ethanol, or various fractions of petroleum distillates, may be employed. As previously indicated, such solvent solutions of toxicant may be emulsi fied with water, if desired. Wetting, emulsifyin and dispersing agents which may be incorporated into the simple solutions or dispersions to accom plish the preparation of such compositions, 1n= clude soaps, salts of sulphonated alcohols, polyglycols, ether-ester complexes, glycerylesters, the metal naphthenates, sulphonated hydrocarbons and their salts, etc.

Finely-divided solids which are adapted tobe employed as carriers for the bromo-alkenes include pyrophyllite, clays, absorptive clay, diatomaceous earth, talc, finely-divided carbon, wood flour, sawdust, volcanic ash, etc.

The following examples illustrate the invention, but are not to be construed as limiting.

EXAMPLE 1 A series of determinations were carried out with various spray and dust compositions containing the bromoalkenes, in which the compositions were applied to the surface of soil and/or litter in small brooder houses. In this operation, soil or litter consisting of shredded cane, straw, etc. was distributed over the floor of the brooder houses to a depth of 3 or 4 inches and thereafter moistened and heavily infected with a suspension of sporulated oocysts of Eimeria tenella. These oocysts constitute an infectious stage of the coccidia. The fumigant compositions, where liquid, were then sprayed upon the surface of the soil or litter. Where dusts were employed, the composition was distributed more or less evenly over the surface of the soil or litter and there after worked lightly into the surface thereof. Twenty-four to forty-eight hours after treatment, the houses were aired and a number of to 12 day old chickens confined therein. Feed was spread on the soil or litter during the first 24 hours of the chickens confinement, and thereafter standard feeding and watering units were made available.

After exposure to the contaminated soil or litter, observations were made to determine whether or not coccidiosis developed in the chickens. This disease runs a typical course. Five days after infection, the droppings are bloody, due to hemorrhage of the damaged cecal mucosa, so that visual observations were indicative of the degree of infection. In each instance, however, the birds were killed and autopsied seven days after having been confined in the brooders, and microscopic examination wasmade of the cecal contents of each bird to determine the degree of cecal damage and the presence or absence of oiicysts in the cecal contents. Both the visual observations of droppings and the examination of the ceca and cecal contents were relied upon in determining the degree of coccidial infection. The following table sets forth the results obgrams of 1.4-dibromo-butene-2 and 244 grams of ethylene dichloride were charged into an aerosol bomb. This mixture was then liberated as an aerosol in a 500 cubic foot brooder house contaminated with Salmonella pulloram and sporulating oocysts of coccidia as described in Example 1. Twenty-four hours after this treatment, the brooder house was thoroughly aired, and 12 day old chicks introduced therein substantially as described in Example 1 Seven days later, the usual observations were made to determine the degree of infection of the chicks. No coccidial infection was found. Also, a complete control of Salmonella palloram was obtained.

pounds per 1000 cubic feet. Sixteen hours after treatment, chicks were exposed to the infective organisms and observed for the development of coccidosis. At all rates of treatment, a complete control was'obtained as regards prevention of tained with representative compositions. coccidial infection in the chicks. Chicks em- Table Autopsy o d o 'r i f hi fi ompoun omposl mn pp 1e Degree Oiicysts Degree of Dwppmgs Cecal in Cecal Coccidial Damage Contents Infection Ailyzl Bromide (0n Litter) 5% (Wt./Vo1.) Trace Very Few. .Trace. 1.3- romo-Propene (On Soil) 10% (Wt./Vol.) Do. Do 10% (Wt/VOL). None. Do 10% (Wt/Vol). Do. 1.4-Dibromo-Butene-2 (On Litter) 1.25% Trace Do None Do Control (On Litter) lA-Dibromo-Butene-Z (011 Control (0n Soil) lA-Dibromo-Butene-Z (On Soil) Control (0n Soil) 1.4-Dibromo-Butene-2 (On Litter).

Abundant Severe.

one

Abundant Severe.

...do. ...do--.. do Do.

1 In ethylene dichloride.

i In Stoddard solvent.

8 In Stoddard solvent-ethylene dichloride mixture. 4 In and on pyrophyllite.

a In and on adsorptive clay.

5 In and on dietomaceous earth.

" In xylene.

EXAMPLE 2 of the 1.4-dibromo-butene-2 per square foot of soil surface. In these operations the Salmonella pullorum was effectively controlled and it was impossible to obtain living cultures from the previously contaminated surfaces.

EXAMPLE 3 In an operation similar to that described in Example 2, 454 grams of methyl bromide, 100

ployed in control determinations were badly infected.

EXAMPLE 5 In a further determination, propene was employed in the treatment of soil infected with coccidia. This operation was carried out by injecting the 1.3-dibromo-propene into the contaminated soil to a depth of approximately 3 inches and on 6 inch centers and thereafter dampening the surface of the soil with Water to provide a water seal. The 1.3-dibromopropene was applied without diluent and in the amounts of 0.3, 0.6 and 1.2 grams per square foot of soil under treatment. Two days following the treatment 2 week old chickens were exposed to contamination from the treated soil. Autopsy of these chickens after a 7 day interval, showed complete prevention of coccidiosis in the opera- .tions employing 0.6 and 1.2 grams of 1.3-dibromopropene per square foot, and only a trace of infection in the operation employing 0.3 gram per square foot. Birds employed in control determinations were heavily infected.

1.3-dibromowherein n is an integer from 3 to 4, inclusive, and a: is an integer from 1 to 2, inclusive, in an amount suificient to provide a. concentration of at least 0.5 gram of the bromo-alkene per square foot of area treated, and thoroughly airing the treated surfaces.

2. A method for preventing the infection of domestic animals and'poult'ry' by coccidia which includes the step of treating the soil, litter, pens, and housing associated with such animals and poultry with 1.4-dibromo-butene-2, in su'fiicient concentration to exert a lethal action upon the infectious organisms and their intermediate life stages.

3. A method for preventing the infection of domestic animals and poultryby coccidia which includes the step of treating the soil, litter, pens. and housing associated with such animals and poultry with 1.3-dibromo-propene, in sufficient concentration to exert a lethal action upon the infectious organisms and their intermediate life stages.

4. A method for preventing the infection of domestic animals and poultry by coccidia which includes the step oftreating the soil, litter, pens, and housing associated with such animals and poultry with allyl bromide, in sufficient concentration to exert a lethal action upon the infectious organisms and their intermediate life stages.

8 A 5. A method for" preventing the infection of domestic animals and poultry by coccidia which includes the step of fumigating the soil, litter, pens, and housing associated with such animals and poultry with a synthetic bromo-alkene of high vapor pressure and having the formula,

wherein n is an integer from 3 to 4, inclusive, and :c is an integer from 1 to 2, inclusive, in the amount of at least 0.2 pound of toxicant per 1,000 cubic feet of space under treatment.

ALFRED E. DOTY. JULIUS E. JO1-Il {SON, JR. DORSEY R MU SSELL. MARK A. WOLF.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,057,044 Meisenburg et a1. Oct. 13, 1936 2,139,102 Steik et a1. Dec. 6, 1938 2,281,239 Hass Apr. 28, 1942 2,316,963 McKee et a1 Apr. 20, 1943 2,403,435 Hammer July 9, 194G, 2,415,251 Leavitt Feb. 4, 1947 2,424,520 Tonkin July 22, 1947 OTHER REFERENCES Lehman, Organic Fumigants for Wireworms," Jour. Econ. Entom. 35, No. 5 (Oct. 1942), 659-661. (Copy in Div. 43.)

Roark 8a Cotton, U. S. Dept. of Agriculture Tech. Bull. No. 162, March 1929, Tests of Various Aliphatic Compounds as Fumigants, pp. 1, 7, 35, 44. (Copy in 167-22.) 

1. A METHOD FOR PREVENTING THE INFECTION OF DOMESTIC ANIMALS AND POULTRY BY COCCIDIA WHICH INCLUDES THE STEPS OF TREATING THE SOIL, LITTER, PENS, AND HOUSING ASSOCIATED WITH SUCH ANIMALS AND POULTRY WITH SYNTHETIC BROMO-ALKENE OF HIGH VAPOR PRESSURE AND HAVING THE FORMULA. WHEREIN N IS AN INTEGER FROM 3 TO 4, INCLUSIVE AND I IS AN INTEGER FROM 1 TO 2, INCLUSIVE, IN AN AMOUNT SUFFICIENT TO PROVIDE A CONCENTRATION OF AT LEAST 0.5 GRAM OF THE BROMO-ALKENE PER SQUARE FOOT OF AREA TREATED, AND THOROUGHLY AIRING THE TREATED SURFACE. 